Pinnacle Technology and Dr. George Wilson of the University of Kansas will design a sensor suite capable of measuring physiologically relevant levels of glutamate, in vivo, in untethered small animals, with high spatial resolution and under ischemic conditions. Research has shown that the major cause of cell death following an ischemic stroke is not hypoxia, but radically elevated levels of glutamate (glutamate excitotoxicity). The ischemic event has been well characterized in terms of blood flow and tissue oxygenation, but other than microdialysis, there is no tool currently available to directly measure glutamate excitotoxicity. Microdialysis is of limited use due to its poor temporal resolution. Electrochemical sensors work well for electroactive species, but not for non-electroactive species. Behavioral scientists also seek to make connections between the brain and behavior. For these studies high spatial resolution is needed. In Phase I, needle-type biosensors (180 mu/m diameter) will be developed to detect large concentrations of glutamate during ischemic conditions. High spatial resolution biosensors (76 mu/m diameter), will also be developed for normal oxygen conditions ( >40 torr). In Phase II, the team will develop a 76 mu/m ischemic glutamate sensor and 10 um glutamate sensors for single-cell measurements and associated electronics.